Biodegradable polyanhydrides have been extensively researched for use as biomaterials for tissue engineering and drug delivery. Most polyanhydrides are biodegradable and biocompatible polymers that undergo hydrolysis in vitro and in vivo to release water-soluble biocompatible degradation products. These polymers completely degrade due to the hydrolytically labile nature of the anhydride bonds and their degradation rate can be controlled by manipulating the polymer composition. Polyanhydrides are predominantly surface eroding, which allows a controlled release, thus avoiding a burst release that can cause non-desirable side effects. All of these features make polyanhydrides useful for delivering biologically active compounds. See Uhrich, K.; et al., Macromolecules 1995, 28, 2184-2193; Uhrich, K.; et al., J. Polym. Sci., Polym. Chem. Ed. 1996, 34, 1261-1269; Langer, R. Acc. Chem. Res. 2000, 33, 94-101; Anastasiou, T.; Uhrich, K. Macromolecules 2000, 33, 6217-6221; Mathiowitz, E., et al., Nature 1997, 386, 410-414; Chasin, M.; Langer, R. Biodegradable polymers as drug delivery systems: New York, 1990; Brem, H., et al., Lancet 1995, 345, 1008-1012; Hanes, J.; Chiba, M.; Langer, R. Biomaterials 1998, 19, 163-172; Leong, K, et al., Biomaterials 1986, 7, 364-371; Leong, K., et al., J. Biomed. Mater. Res. 1986, 20, 51-64; Sanders, A., et al., Polym. Prepr. 1999, 40, 888; Gopferich, A.; Tessmar, J. Adv. Drug Del. Rev. 2002, 54, 911-931; Gopferich, A. Biomaterials 1996, 17, 103-114; Whitaker-Brothers, K.; Uhrich, K. J. Biomed. Mater. Res. 2004, 70A, 309-318; Prudencio, A.; Schmeltzer, R. C.; Uhrich, K. E. Macromolecules 2005, 38, 6895-6901; Von Burkersroda, F.; Schedl, L.; Gopferich, A. Biomaterials 2002, 23, 4221-4231; Tamada, J.; Langer, R. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 552-556; and Quick, D.; and Macdonald, K.; Anseth, K. J. Control. Rel. 2004, 97, 333-343.
Previously, Erdmann et al. reported the synthesis of a poly(anhydride-ester) comprised of salicylic acid (SA) as a novel degradable biomaterial in which the drug, i.e. SA, is chemically incorporated into the polymer backbone and not attached as a side group or physically admixed. This unique system releases a high load of salicylic acid and sebacic acid upon hydrolysis of the ester and anhydride bonds in the backbone.
Phenolic compounds have been known for their wide biological activity, among which their antioxidant and antimicrobial activities stand out. Copolyesters containing natural non-toxic phenolic derivatives such as vanillic acid (VA) and syringic acid (SGA) were previously prepared and their mechanical properties studied (see Nagata, M., J. Applied Polymer Sci. 2000, 78, 2474-2481; Kricheldorf, H., et al., Polymer 1995, 36, 1697-1705; and Fan, J. et al., J. Applied Polymer Sci. 2006, 100, 1214-1221). However no study on the phenolic derivative release from these copolyesters was reported. See San Roman, J., et al., J. Biomed. Mater. Res. 1996, 32, 19-27; Sato, H., et al., Biomater. Sci. Polymer. Ed. 1991, 2, 1-13; Elvira, C., et al., Polymer 1999, 40, 6911-6924; Chafi, N.; Montheard, J.; Vergnaud, J. Int J Pharm 1989, 52, 203-211; Rivas, B., et al., J. Membrane Sci. 2001, 192, 187-191; and Elvira, C.; San Roman, J. J. Mater. Sci.: Mater. in Med. 1997, 8, 743-746.
In spite of the above disclosures, there remains a need for novel materials that can be applied to a wide range of applications. For example, there is a need for fast degrading polymers that can be used to deliver biologically active compounds via topical administration.